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Lysosome Dysfunction Enhances Oxidative Stress‐Induced Apoptosis through Ubiquitinated Protein Accumulation in Hela Cells

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Abstract

The role of lysosomal system in oxidative stress‐induced apoptosis in cancer cells is not fully understood. Menadione is frequently used as oxidative stress model. It is indicated that menadione could induce autophagy in Hela cells. In the present study, we examined whether the lysosomal inhibitor, ammonium chloride (NH4Cl) could prevent the autophagy flux by inhibiting the fusion of autophagosomes with lysosomes and enhance apoptosis induced by menadione via mitochondrial pathway. The results demonstrated generation and accumulation of reactive oxygen species and increased levels of ubiquitinated proteins and GRP78 in cells treated with both menadione and NH4Cl. Our data indicates that lysosomal system through autophagy plays an important role in preventing menadione‐induced apoptosis in Hela cells by clearing misfolded proteins, which alleviates endoplasmic reticulum stress. Anat Rec, 2013. © 2012 Wiley Periodicals, Inc.
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Document Type: Research Article

Affiliations: 1: Pharmacology Laboratory, Affiliated Hospital of Changchun University of Traditional Chinese Medicine, Changchun, China 2: Medical Research Laboratory, Jilin Medical College, Jilin City, China 3: Department of Pathophysiology, Norman Bethune College of Medicine, Jilin University, Changchun, China 4: Department of Pathology, Basic Medical College, BeiHua University, Jilin City, China

Publication date: January 1, 2013

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